Abstract
Purpose:
Leber’s Hereditary Optic Neuropathy (LHON) patients mostly carry three mitochondrial DNA point mutations, m.3460 G>A, m.11778 G>A and m.14484 T>C, occurs in the genes encoding complex I subunits of the respiratory chain. Over 95% of LHON pedigrees harbor one of these three primary mitochondrial DNA mutations. The aim of this study was to screen whole mitochondrial genome of LHON patients to explore the role of primary mutations and other mtDNA variants in the pathogenesis of disease
Methods:
Thirty five LHON patients and thirty five age matched controls were recruited for the study from the Neuro-ophthalmology clinic, Aravind Eye Hospital, Madurai, Tamil Nadu, India. Long PCR based nine pairs of primer were used to amplify whole mitochondrial genome of both the cases and controls. Bidirectional sequencing was performed with thirty one different primers. The sequences from patients and controls were compared with the revised Cambridge reference sequence (rCRS NC_012920). The observed variations were compared with mitochondrial databases such as Mitomap (http://www.mitomap.org); mtDB (http://www.genpat.uu.se/mtDB) and HmtDB (http://www.hmtdb.uniba.it:8080/hmdb) for their significance
Results:
Out of thirty five LHON patients screened, ten patients reported with the m.11778G>A mutation and one with m.14484T>C mutation. We could not identify m.3460G>A mutation in any of the patients. Along with these primary mutations, we have identified non synonymous variations in protein coding genes in both the cases and controls. Known disease associated variants were also identified in this study
Conclusions:
Two primary mutations (m.11778G>A and m.14484T>C), non synonymous mutations and other mitochondrial disease associated variants were also identified in this study. Better characterization of the relationship between mitochondrial DNA mutations background and optic nerve dysfunction will result in improved genetic counseling and development of therapeutic strategies.
Keywords: 613 neuro-ophthalmology: optic nerve •
537 gene screening •
539 genetics